Angiotensin II: A double-edged sword in inflammation

Clinical and basic research has increased our knowledge of the actions of t he vasoactive hormone angiotensin II (Ang II), showing that it has multifun ctional properties beyond its hemodynamic effects. It is commonly accepted that Ang II is a growth factor that participates in pathological settings, including renal diseases. However, a new aspect of this peptide is coming i nto focus: its potential role as a proinflammatory modulator. In this revie w, we summarize the apparently confusing information about the properties o f Ang II and discuss its relations to the inflammatory process, as well as the potential mechanisms mediated by activation of nuclear transcription fa ctors. Ang II seems to participate in the key events of the inflammatory re sponse: First, it increases vascular permeability (via prostaglandins and v ascular endothelial cell growth factor/vascular permeability factor) thus i nitiating the inflammatory process. Second, it participates in the recruitm ent of infiltrating cells into the tissues through direct activation of the inflammatory cells or by regulation of the expression of adhesion molecule s and chemokines by resident cells. Finally, Ang II may contribute to tissu e repair by regulation of cell growth and matrix synthesis. The renin-angio tensin system (RAS) thus appears to serve as a vascular inflammatory regula tor and may even participate in immunologically-induced inflammation. Howev er, more often activation of the RAS has an undesirable outcome, such as ov erhealing, because the inflammatory repair response itself involves a funct ionally imperfect system.